Caroline B Appleyard

Ponce Health Sciences University - Ponce Research Institute

Inflammatory Bowel Diseases (IBD) either Crohn’s disease or Ulcerative colitis are debilitating disorders that affect the gastrointestinal tract with chronic inflammation. Patients with IBD are often characterized by having a change in the gut microbiome composition and decreased levels of vitamin D, which contribute to disease development. Because...

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue in areas outside the uterus. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), inflammation, and implanted endometrial vesicles, which are all decreased by voluntary exercise. Interesti...

Introduction We have previously shown that Environmental Enrichment (EE)-consisting of social support, novelty, and open spaces—decreased disease progression and anxiety in a rat model of endometriosis. We developed a novel EE intervention to be tested in a pilot randomized clinical trial (RCT) in patients with endometriosis, a painful, stressful d...

High-fat diet (HFD) is associated with gut microbiome dysfunction and mental disorders. However, the time-dependence as to when this occurs is unclear. We hypothesized that a short-term HFD causes colonic tissue integrity changes resulting in behavioral changes. Rats were fed HFD or low-fat diet (LFD) for a month and gut microbiome, colon, and beha...

Introduction: Endometriosis is a complex gynecological disorder characterized by the ectopic growth of endometrial tissue. Symptoms of endometriosis are known to impair the quality of life of patients, among these symptoms are dysmenorrhea, chronic pelvic pain, and gastrointestinal (GI) issues. These GI issues are one of the common reasons for mis...

Endometriosis, an estrogen dependent disease, is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity resulting in pain and discomfort. Estrogen plays an important role in the growth and persistence of endometriotic tissue along with inflammation. Estrogen receptor alpha (ERα) expression is significa...

Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal a...

Introduction Endometriosis is a chronic gynecological disorder characterized by the growth of endometrial glands and stroma outside the endometrial cavity producing inflammation and pain. Previously we demonstrated that modulation of the hypothalamic pituitary adrenal (HPA) axis exacerbates the development and severity of this condition. A physical...

Introduction Monitoring the impact of natural disasters such as pandemics on health and wellbeing is a public health priority. Stress is proven to affect pain intensity and quality of life of endometriosis patients. A cross-sectional study was conducted to determine whether the measures implemented to mitigate COVID-19 infections had a substantial...

Endometriosis is a complex disease characterized by inflammation and the growth of endometrial- like glands and stroma outside the uterine cavity. The pathophysiology of endometriosis is not entirely understood, however, with a prevalence of ~10% of women in their reproductive years, the disease symptoms significantly affect the quality of life of...

We previously demonstrated the negative impact of stress in an animal model of endometriosis. Although its role is unclear, altered levels of vitamin D (VitD) have been found in patients with this condition. VitD signaling through the VitD receptor (VDR) has anti-proliferative properties and induces an anti-inflammatory phenotype in macrophages. We...

There is strong evidence from humans and animal models showing that abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and/or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems, contributing to disease. Stress is known to affect the physiology of pelvic organs and to disturb th...

Endometriosis is a chronic inflammatory disorder in which endometrial tissue is found outside the uterine cavity. Previous reports suggest that there is a dysregulation of the hypothalamic pituitary adrenal axis during the progression of endometriosis. Our previous report showed that a short-term treatment with antalarmin, a corticotrophin releasin...

Even though HIV-1 replication can be suppressed by combination antiretroviral therapy (cART) inflammatory processes still occur, contributing to comorbidities. Comorbidities are attributed to variety of factors, including HIV-1 mediated inflammation. Several HIV-1 proteins mediate central nervous system (CNS) inflammation, including Nef. Nef is an...

Endometriosis is a painful gynecological disease with no cure and limited therapeutic options. It has been hypothesized that epigenetic drugs can be used as a nonhormonal treatment for endometriosis. This study was conducted to study the efficacy of an inhibitor of the histone methyltransferase EZH2 using an established rat model of endometriosis....

Endometriosis is a disorder in which endometrial tissue is found outside the uterus causing pain, infertility and stress. Finding effective, non-hormonal and long-term treatments for endometriosis still remains one of the most significant challenges in the field. Corticotropin releasing hormone (CRH) is one of the main signaling peptides within the...

Morphological characteristics of endometriosis vesicles illustrated by the stage of estrous cycle at sacrifice. (A) Percent developed vesicles. (B) Group means of the total vesicle weight per rat. (C) Group means for the total vesicle volume per rat. (D) Group means for the total vesicle area per rat. The table illustrates the statistical results o...

Estrous cycle distribution for experiment 1 and experiment 2. (A) The number of rats that were at each stage of the estrous cycle the day of behavioral testing and sacrifice for experiment 1. Estrous cycle before endometriosis surgery was not assessed in these rats. (B) Estrous cycle in rats for experiment 2 was assessed for 10 days prior to induct...

Anxiety behaviors at 7 days after endometriosis induction surgery for experiment 1. Estrous cycle stage at the time of sacrifice was measured by vaginal smear. We did not pre-planned to sacrifice at any particular stage of the cycle but rather at exactly 7 days after the endometriosis induction. (A and B) Total distance traveled in the open field a...

Anxiety behaviors at 60 days after endometriosis induction or sham surgery for experiment 2. Similar to experiment 1, estrous cycle stage at the time of sacrifice was measured by vaginal smear. We did not pre-planned to sacrifice at any particular stage of the cycle but rather at 60 days after the endometriosis induction. (A and B) Total distance t...

Endometriosis is a disorder in which endometrial tissue is found outside the uterus causing pain, infertility and stress. Finding an effective and long-term treatment for endometriosis still remains one of the most significant challenges in the field. Corticotropin releasing hormone (CRH) is one of the main signaling peptides within the hypothalami...

Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger...

Purpose: We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations. Methods:...

The probiotic mixture VSL#3 attenuates colitis in patients with Inflammatory Bowel Disease (IBD) and in animal models of this condition, but the mechanisms involved are incompletely understood. VSL#3 alters macrophage morphology and secretory profile in vitro in a polarization-dependent manner. We examined the effect of VSL#3 on macrophages in acut...

Purpose: Pain in patients with endometriosis is considered a significant source of stress but does not always correlate with severity of the condition. We have demonstrated that stress can worsen endometriosis in an animal model. Here, we tested the impact of a psychological stress protocol on pain thresholds and pain receptors. Methods: Endomet...

Our review focuses on the colonic macrophage, a monocyte-derived tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as Inflammatory Bowel Disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focu...

Abstract Background: Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory conditions of unknown cause and likely result from the loss of immunological tolerance, which leads to over-activation of the gut immune system. Gut macrophages and dendritic cells (DCs) are essential for maintaining tolerance, but can also contribute to the i...

Studies have examined how endometriosis interacts with the nervous system, but little attention has been paid to opioidergic systems, which are relevant to pain signaling. We used the autotransplantation rat model of endometriosis and allowed to progress for 60 days. The brain was collected and examined for changes in endogenous opioid peptides, mu...

Aim: To determine serum vitamin D levels and colonic vitamin D receptor (VDR) expression in inflammatory bowel disease (IBD) and non-IBD patients and correlate these with histopathology. Methods: Puerto Rican IBD (n = 10) and non-IBD (n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire...

Background: Early life stress has been associated with increasing the risk of developing gastrointestinal disorders by disrupting the brain-gut axis function. Maternal separation (MS) in rats is a well-studied model of early life stress and has been linked to inflammation in adulthood in conditions such as inflammatory bowel disease and irritable b...

Background: Symptoms of endometriosis, such as pain and infertility, are considered significant sources of stress. In many chronic conditions, exercise can act as a stress buffer and influence pain perception. We tested the impact of swimming exercise on pain perception and pain receptors in an animal model of endometriosis. Methods: Endometrios...

The conventional approach of double immunostaining to visualize more than one protein in tissues or cells using antibodies from two different host species is not always feasible due to limitations with antibody availability. Previously reported methodologies for performing multiple immunostains on the same tissue or cells with antibodies originatin...

The use and validity of the Graduate Record Examination General Test (GRE) to predict the success of graduate school applicants is heavily debated, especially for its possible impact on the selection of underrepresented minorities into science, technology, engineering, and math fields. To better identify candidates who would succeed in our program...

Puerto Rico Physiological Society has been conducting PhUn Week activities in schools located in the south of the Island. This year junior students received talks and participated in hands-on activities related to several topics in physiology. Aim: The main was to provide information on basic physiological concepts, what scientists do, and how to p...

To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sp...

Barriers persist in the development and delivery of effective cancer therapies to under-represented minority populations. In Puerto Rico, cancer is the second leading cause of death, yet cancer research awareness and training opportunities remain somewhat limited on the island. These limitations hinder progress toward decreasing the cancer health d...

We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim st...

Background: Patients with Inflammatory Bowel Disease (IBD), most commonly Crohn's disease (CD) or ulcerative colitis (UC), suffer from chronic intestinal inflammation of unknown etiology. Increased proinflammatory macrophages (M1) have been documented in tissue from patients with CD. Anti-inflammatory macrophages (M2) may play a role in UC given t...

Women with endometriosis have significant emotional distress; however, the contribution of stress to the pathophysiology of this disease is unclear. We used a rat model of endometriosis to examine the effects of stress on the development of this condition and its influence on inflammatory parameters. Female Sprague-Dawley rats were subjected to swi...

To investigate the role of epidermal growth factor receptor (EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib. Sprague-Dawley rats received trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol, ic), followed 6 wk later by reactivation with TNBS (5 mg/kg, iv) for 3 d. To induce colitis-associated dysplasi...

Evidence supports involvement of microflora in the transition of chronic inflammation to neoplasia. We investigated the protective efficacy of the probiotic VSL#3 in a model of colitis-associated colorectal cancer. Chronic colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS), followed 6 wk later by sy...

385 Background: Effective prevention of colitis-associated cancer still needs to be achieved. There is evidence that the microflora plays an important role in the progression of chronic inflammation to neoplastic transformation, so the aim of this study was to evaluate the potential efficacy of the probiotic VSL#3 in preventing this transition. Met...

Background: The underlying mechanisms in ulcerative colitis-associated dysplasia are poorly understood. Neurokinin-1 receptors (NK-1R) have been shown to be involved in chronic colonic inflammation, and we have demonstrated their over-expression in patients with dysplasia. The NK-1R has been found to crosstalk with the epidermal growth factor recep...

Compositional changes within the normal intestinal microbiota have been associated with the development of various intestinal inflammatory disorders such as pouchitis and inflammatory bowel diseases (IBD). Therefore, it has been speculated that manipulation of a dysbiotic intestinal microbiota has the potential to restore microbial homeostasis and...